Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension

Structural remodelling of pulmonary vessels is an important feature of pulm onary hypertension (PH), which reflects distal artery muscularization and m atrix remodelling. The matrix metalloproteinases (MMPs) are involved in ext racellular matrix turnover and hence, in smooth muscle cell migration and e ndothelial cell migration and proliferation. Among the MMPs, gelatinases (M MP-2 and MMP-9) can degrade basement membrane components and promote cell p roliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-2 activity, spe cific to pulmonary vessels. Increased MMP-2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonst rated upregulation of MMP-2 messenger ribonucleic acid. Immunolocalization showed MMP-2 throughout the pulmonary vasculature, from the trunk to the di stal vessels, with strong staining of the intima, media and adventitia. MMP -2 was found in its active form and gelatinolytic activity was correlated t o PH severity. Activity localization by in situ zymography corroborated wit h the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-2 act ivity is increased in pulmonary vessels during progression of pulmonary hyp ertension, probably as a result of involvement in the matrix turnover assoc iated with vascular remodelling during pulmonary hypertension.